Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Eur J Pharm Sci. 2022 Oct 1;177:106266. doi: 10.1016/j.ejps.2022.106266. Epub 2022 Jul 19.
Combined intravenous and intrathecal administration of norvancomycin (NVCM) is routinely employed in treating methicillin-resistant Staphylococcus aureus (MRSA) ventriculitis in patients following craniotomy. However, the optimal dosing regimen, the pharmacokinetics (PK) of NVCM in cerebrospinal fluid (CSF), and the clinical outcome are yet to be elucidated. Herein, a single-center randomized controlled trial was conducted in the Neurosurgery Department of the Second Hospital of Hebei Medical University (Shijiazhuang, China). Patients with MRSA ventriculitis after craniotomy were randomly assigned to two groups. The control group received 800 mg NVCM intravenously every 12 h, and the experimental group received 800 mg NVCM intravenously every 12 h and 16 mg NVCM intrathecal administration every 24 h. The primary outcome was the length of therapy, while the secondary outcomes included the area under the concentration-time curve in 0-24 h/minimum inhibitory concentration ratio (AUC/MIC) of NVCM in CSF. A total of 29 patients (14 in the experimental group and 15 in the control group) were included in this study. Of these, 24 constituted the final analysis population, with 12 in each group. The average length of therapy in the experimental group was markedly shorter than that of the control group (11.2 ± 2.6 days vs. 16.6 ± 5.2 days, P = 0.005), while the AUC/MIC in the experimental group was significantly higher than that in the control group (2306.57 ± 928.58 vs. 46.83 ± 27.48, P < 0.001) with no increase in adverse reactions. Combined intravenous and intrathecal administration can shorten the treatment time of intracranial infection without higher adverse reaction risks in our research. Further studies with larger sample size are warranted to verify its safety and efficacy.
静脉联合鞘内注射去甲万古霉素（NVCM）是治疗颅脑手术后耐甲氧西林金黄色葡萄球菌（MRSA）脑室炎的常规方法。然而，其最佳剂量方案、NVCM 在脑脊液（CSF）中的药代动力学（PK）以及临床疗效仍有待阐明。本研究在河北医科大学第二医院神经外科进行，采用单中心随机对照试验，将颅脑手术后 MRSA 脑室炎患者随机分为两组。对照组给予 800mg NVCM 静脉滴注，每 12h 一次；实验组给予 800mg NVCM 静脉滴注，每 12h 一次，同时鞘内注射 16mg NVCM，每 24h 一次。主要结局为治疗时间，次要结局包括 NVCM 在 CSF 中的 0-24 小时浓度-时间曲线下面积与最小抑菌浓度比值（AUC/MIC）。共纳入 29 例患者（实验组 14 例，对照组 15 例），其中 24 例进入最终分析人群，每组 12 例。实验组的平均治疗时间明显短于对照组（11.2±2.6 天比 16.6±5.2 天，P=0.005），实验组 AUC/MIC 明显高于对照组（2306.57±928.58 比 46.83±27.48，P<0.001），且不良反应无增加。在本研究中，静脉联合鞘内注射可以缩短颅内感染的治疗时间，且不良反应风险没有增加。需要更大样本量的进一步研究来验证其安全性和有效性。
